Chloral reactions

Trichloromethyl substituted thiazolidines have been prepared from chloral. Reaction of chloral with anilines afforded the corresponding imines which were then treated in situ with thioglycolic acid to give a series of 2-trichloromethyl substituted thiazolidinones <96HC227>. 

Chloride initiation of chloral polymerization could be readily achieved with tetraalkyl ammonium chlorides, such as tetrabutyl ammonium chloride, or with trialkyl sulphonium chlorides as initiators. Chloral polymerization initiated with R4NCI behaved very similarly to that with tertiary amine initiation. It is likely that the actual initiator of chloral polymerization with tertiary amines was chloride ion, which was presumably formed by chloride abstraction from chloral by the amine. The ease of chloride exchange in chloral reactions was demonstrated by initiation studies with Cl as initiator. 

Ene reactions. Chloral has been found to undergo the ene reaction with mono-, 1,1-di-, and 1,2-disubstituted alkenes. The ene reaction in general requires temperatures of about 100° to proceed and is usually not subject to acid catalysis however, in the chloral reaction, several Lewis acids have been found to be effective catalysts FeCU, AICI3, SnCU. 

Isocyanide reaction. Since chloral hydrate is readily converted into chloroform by alkali, it will give the isocyanide reaction. To a few crystals of the solid add about 5 ml. of alcoholic NaOH solution and a few drops of aniline, and heat the disagreeable odour of phenyl isocyanide, C H(NC, is rapidly detected. 

The student is recommended to carry out the following reactions with chloral hydrate in order to familiarise himself with its general properties. 

Fit a 1500 ml. bolt-head flask with a reflux condenser and a thermometer. Place a solution of 125 g. of chloral hydrate in 225 ml. of warm water (50-60°) in the flask, add successively 77 g. of precipitated calcium carbonate, 1 ml. of amyl alcohol (to decrease the amount of frothing), and a solution of 5 g. of commercial sodium cyanide in 12 ml. of water. An exothermic reaction occurs. Heat the warm reaction mixture with a small flame so that it reaches 75° in about 10 minutes and then remove the flame. The temperature will continue to rise to 80-85° during 5-10 minutes and then falls at this point heat the mixture to boiling and reflux for 20 minutes. Cool the mixture in ice to 0-5°, acidify with 107-5 ml. of concentrated hydrochloric acid. Extract the acid with five 50 ml. portions of ether. Dry the combined ethereal extracts with 10 g. of anhydrous sodium or magnesium sulphate, remove the ether on a water bath, and distil the residue under reduced pressure using a Claiseii flask with fractionating side arm. Collect the dichloroacetic acid at 105-107°/26 mm. The yield is 85 g. 

Dichloroacetic acid is produced in the laboratory by the reaction of chloral hydrate [302-17-0] with sodium cyanide (31). It has been manufactured by the chlorination of acetic and chloroacetic acids (32), reduction of trichloroacetic acid (33), hydrolysis of pentachloroethane [76-01-7] (34), and hydrolysis of dichloroacetyl chloride. Due to similar boiling points, the separation of dichloroacetic acid from chloroacetic acid is not practical by conventional distillation. However, this separation has been accompHshed by the addition of a eotropeforming hydrocarbons such as bromoben2ene (35) or by distillation of the methyl or ethyl ester. 

Make acid yields coumaUc acid when treated with fuming sulfuric acid (19). Similar treatment of malic acid in the presence of phenol and substituted phenols is a facile method of synthesi2ing coumarins that are substituted in the aromatic nucleus (20,21) (see Coumarin). Similar reactions take place with thiophenol and substituted thiophenols, yielding, among other compounds, a red dye (22) (see Dyes and dye intermediates). Oxidation of an aqueous solution of malic acid with hydrogen peroxide (qv) cataly2ed by ferrous ions yields oxalacetic acid (23). If this oxidation is performed in the presence of chromium, ferric, or titanium ions, or mixtures of these, the product is tartaric acid (24). Chlorals react with malic acid in the presence of sulfuric acid or other acidic catalysts to produce 4-ketodioxolones (25,26). 

A novel type of ring closure is the reaction of 6-amino-5-dichloroacetylaminopyrimidines (285) with sulfur and morpholine under the conditions of a Kindler reaction (B-64MI21605). 7-Morpholinopteridin-6-ones (287) are formed, either via thiooxamide derivatives (286) or via corresponding 7,8-dihydropteridines (284 equation 102). Chloral hydrate also reacts with 2-substituted 5,6-diaminopyrimidin-4-ones to form pteridin-6-ones (56JCS3311, 64JCS565) by a so far unknown mechanism. 

Adolph Baeyer is credited with the first recognition of the general nature of the reaction between phenols and aldehydes in 1872 ([2,5-7] [18], Table 5.1). He reported formation of colorless resins when acidic solutions of pyrogallic acid or resorcinol were mixed with oil of bitter almonds, which consists primarily benzaldehyde. Baeyer also saw resin formation with acidic and basic solutions of phenol and acetaldehyde or chloral. Michael and Comey furthered Baeyer s work with additional studies on the behavior of benzaldehyde and phenols [2,19]. They studied a variety of acidic and basic catalysts and noted that reaction vigor followed the acid or base strength of the catalyst. Michael et al. also reported rapid oxidation and darkening of phenolic resins when catalyzed by alkaline materials. 

Most of the compounds in this class have been prepared from preexisting crown ether units. By far, the most common approach is to use a benzo-substituted crown and an electrophilic condensation polymerization. A patent issued to Takekoshi, Scotia and Webb (General Electric) in 1974 which covered the formation of glyoxal and chloral type copolymers with dibenzo-18-crown-6. The latter were prepared by stirring the crown with an equivalent of chloral in chloroform solution. Boron trifluoride was catalyst in this reaction. The polymer which resulted was obtained in about 95% yield. The reaction is illustrated in Eq. (6.22). 

Polyhalodiethyl ethers are also formed in the reaction of sulfur tetrafluoride with perhaloacetaldehydes in the case of chloral, a chlorine-fluorine rearrangement occurs [I7Q] (equations 82 and 83). 

Reactions.—i. Add a few drops of a solution of chloral hydrate to a little ammonio-silver nitrate solution and waiin. Metallic silver will be deposited. 

Caffeine, 131 ( arbamide, 126 Carbamine reaction, 71 Carbolic acid, 179 Carbon, qualitative analysis t Carbon, quantitative analysis 4 Carlus method, 22, 28 Chaiitiway s Xi QX o 174 Chloracetic acid, S7 Chloral, 99 Chloral hydrade, 99 ( hlorbydrin, tii / Chlorobenzoic acid, 166 < hlorofonTi, 70 / Chlorutulueiie, 16 ... 

A few other aldehydes have been used in the reaction, either under normal or pseudo-physiological conditions. Of these, glycolalde-hyde, 5-hydroxypentanal, phenylacetaldehyde, and benzalde-hyde condense readily, but hydroxy and methoxy derivatives of these aromatic aldehydes give the product in poor yield,presumably due to their instability, as evidenced by their tendency to undergo self-condensation in acid solution. Reaction with phthaldehydic acids, such as opianic acid, proceeded readily, whereas reaction with chloral did not occur,... 

Other aldehydes which have been used in the reaction are pro-panal, butanal, glycolaldehyde, 3-hydroxybutanal, and a number of phenylacetaldehydeand benzaldehyde derivatives. Whereas condensation of tryptophan with acetaldehyde takes place even at room temperature and pH 6.7, the reactions with chloral, chloroacetaldehyde, and crotonaldehyde fail entirely. 

The addition of water across carbon-carbon double bonds, a reaction thoroughly investigated by Lucas and Taft, requires strong activation and is catalyzed by hydrogen ions and hydroxyl ions. Addition of water across the 0= =0 bond of aldehydes has also been studied kinetically. Whereas chloral and formaldehyde are largely hydrated (at equilibrium in dilute aqueous solution), acetaldehyde and other... 

With aldehydes some diaziridines condense under the conditions of preparation. The formation of a fused triazolidine ring occurs regularly if aldehydes are treated with ammonia and chloramine to give diaziri-dines [Eq. (39)]. If, however, chloral is added previously to the reaction mixture, the 3-aIkyl-diaziridines (45) arc caught as their chloral adducts. By the alkali fission of these chloral adducts, 3-alkyl-diaziridines, e.g. (45), can be prepared. 

A similar reaction of y-bromopropyl derivatives under the influence of silver nitrate was described by Kohn as early as 1904. The 3-hydroxyketone formed from chloral and acetophenone can react with a chlorocarbamate to yield a pseudourethane which is probably a 4-hydroxy-2-0X0 tetrahydro-l,3-oxazine. ... 

Reaction of o-toluidine with chloral hydrate in presence of hydroxylamine hydrochloride and subsequent treatment with H2SO4 gave the isatin derivative 337. Bromination of 337 followed by reaction with sodium diethyl malonate gave 338. Catalytic reduction with Pd/C gave the oxoindole derivative 339 that upon hydrolysis with aqueous NaOH followed by... 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

Accoiiding to Hanriot ionone can be detected in very minute amount by the following reaction If traces of it be dissolved in concentrated hydrochloric acid, the liquid becomes of an intense golden colour, and if the solution he warmed with chloral hydrate, a dirty violet colour results. The violet colouring matter is extracted by ether, and if the ether be evaporated a water-soluble violet-coloured residue is left. This test will detect 1 part of ionone in 2b00. 

An intimate mixture of betaine hydrate (67.5 g) and chloral hydrate (100 g) was warmed to ca. 60°C when an exothermic reaction occurred and the mixture became pasty. It was then stirred at 60°C for 30 minutes. The residue solidified on cooling and was crystallited from a small amount of water. The product separated in hard, colorless prisms of MP 122.5° to 124.5°C (corr). 

Chirality center, 292 detection of, 292-293 Eischer projections and, 975-978 R,S configuration of, 297-300 Chitin, structure of, 1002 Chloral hydrate, structure of, 707 Chloramphenicol, structure of, 304 Chlorine, reaction with alkanes, 91-92,335-338 reaction with alkenes, 215-218 reaction with alkynes, 262-263 reaction with aromatic compounds, 550 Chloro group, directing effect of, 567-568... 

A closely related reaction has been performed with other aldehydes and even with ketones without a catalyst, but with heat. The aldehydes and ketones here are active ones, such as chloral and acetoacetic ester. The product in these cases is a 3-hydroxy alkene, and the mechanism is pericyclic ... 

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